Pfizer Asks F.D.A. to Clear 2 Vaccine Doses for Young Children as a Start

WASHINGTON — Pfizer and its partner, BioNTech, asked the Food and Drug Administration on Tuesday to authorize two doses of their coronavirus vaccine for children younger than 5 while the companies continue to research whether three doses would be more effective for the age group.

In a highly unusual move, federal regulators pressed the companies to submit the request even though two doses failed to produce the hoped-for immune response among children 2 to 4 years old in a clinical trial. Only children between 6 months and 2 years old demonstrated an immune response comparable to that of older teenagers and young adults, the standard for a successful trial.

The request for emergency authorization comes as the highly contagious Omicron variant has led to record numbers of infections. The under-5 group includes more than 19 million children, the only Americans not yet eligible for vaccination.

The disappointing trial results, announced in December, prompted the companies to test a third low dose of the shot in that age group. But rather than wait until the end of March for the results, federal regulators decided to encourage Pfizer to apply for authorization of a two-dose regimen now in hopes of getting a head start on the vaccination effort.

In meetings about the strategy, government officials argued that two doses had proved safe, even if they failed to produce an immune response in the whole age group, according to multiple people familiar with the discussions. Children in the trial received one-tenth of the adult dose.

If children can get an initial injection this month, some officials reasoned, they will be ready for a third dose by the time researchers get what they hope will be successful results from the three-dose trial. The first two doses would be spaced three weeks apart, followed by a third dose two months after the second.

Dr. Janet Woodcock, the acting F.D.A. commissioner, and Dr. Peter Marks, an agency regulator who oversees its vaccines office, said on Tuesday that it was important to act quickly given the surge in Omicron cases, which has now peaked in many parts of the country, and the likelihood that other variants would follow.

An emergency meeting of the F.D.A.’s advisory group of outside experts is scheduled for Feb. 15, when they will discuss the request and make a recommendation. In an interview Tuesday, Dr. Paul A. Offit, a member of the group and director of the Vaccine Education Center at Children’s Hospital of Philadelphia, suggested that regulators could be short-circuiting the normal process without a clear rationale.

“It doesn’t make sense we would approve a two-dose vaccine on the assumption the third dose would make up for deficiencies of the two doses,” he said.

Albert Bourla, Pfizer’s chairman and chief executive, said in a statement that “ultimately, we believe that three doses of the vaccine will be needed for children 6 months through 4 years of age to achieve high levels of protection against current and potential future variants.” But he said that if two doses are authorized in the meantime, “parents will have the opportunity to begin a Covid-19 vaccination series for their children while awaiting potential authorization of a third dose.”

Pfizer and BioNTech’s study of younger children was intended to measure immune responses, not the vaccine’s efficacy in preventing infections or severe cases of Covid-19. But because some children in the trial became infected, researchers got indications of how well the vaccine worked to stave off the virus, two people familiar with the study said. A similar development occurred in the companies’ study of their vaccine in 5- to 11-year-olds, which overlapped with a crushing wave of the Delta variant.

One person familiar with the data, who spoke on condition of anonymity, said children 2 to 4 years old who were given two shots were infected at a rate 57 percent lower than the children in the placebo group. Children 6 months to 2 years old who got shots were infected at a rate 50 percent lower than the placebo group. There were fewer than 100 cases of symptomatic infection — a small fraction of the participants overall — and the margins of error were wide, that person said.

The data also suggested that the vaccine better protected the children against infection from Delta than from Omicron. Omicron is better than Delta at evading the protection of both the Pfizer-BioNTech and Moderna vaccines in adults.

The regulators’ strategy seemed based in part on the likelihood that the Pfizer-BioNTech’s three-dose trial would prove successful. Several experts, including Dr. Yvonne Maldonado, a Stanford professor of pediatric infectious diseases, said the history of vaccines suggested that a third dose would, in fact, enhance the immune response.

“There’s almost no conceivable hypothesis where a third dose would be worse,” said Dr. Maldonado, a lead investigator at the Stanford site of Pfizer-BioNTech’s pediatric vaccine trials. “At worst it could be no different. So it might just be that two doses is the best you’re going to get.”

Dr. H. Cody Meissner, another member of the F.D.A. advisory committee and chief of the pediatric infectious diseases division at Tufts Children’s Hospital, said he was open minded about the F.D.A.’s approach. But he said he worried about whether rare side effects might be missed in small-scale trials. The Pfizer-BioNTech trial included about 1,200 children younger than 2, and about 1,500 between 2 and 4, according to people familiar with the study’s design.

The panel’s decision “will partly depend on what are the rates of hospitalization and severe disease in this age group,” Dr. Meissner said, “and what our sense is in terms of potential harm” should the two-dose regimen be authorized.

If the F.D.A. moves ahead with authorization, a separate advisory panel to the Centers for Disease Control and Prevention will vote on whether to support the action. Dr. Rochelle Walensky, the agency’s director, will then decide whether the C.D.C. should recommend the shots as government policy.

The public deliberations of the regulatory agencies’ expert committees could influence uptake of the vaccine, underscoring the importance of a clear and open discussion of what the data shows. If the shots are authorized, families may still proceed with caution. Three in 10 parents of children younger than 5 now say they intend to get their children vaccinated against the coronavirus as soon as shots become available for that age group, according to a survey published Tuesday by the Kaiser Family Foundation.

In meetings about the plan, government officials argued that an unorthodox approach was necessary. Dr. Marks, who oversees the F.D.A.’s vaccine division, said in a statement on Tuesday: “The need for a safe and effective vaccine for our youngest children is significant, particularly given the rapid spread of the Omicron variant, the notable rise in the number of hospitalizations in young children with severe disease and the possibility that future variants could cause severe disease in those who are unvaccinated.”

Dr. Maldonado, the Stanford professor, said that even a more modestly effective vaccine for young children could be valuable in this phase of the pandemic. On the other hand, with the Omicron wave peaking in many parts of the country, regulators might face more criticism that they are unnecessarily rushing the process at a time when children might be less at risk of infection.

The rate at which children under 5 were admitted to hospitals with Covid-19 began rising around mid-December, then peaked in early January, according to C.D.C. data. But as of Jan. 22, the weekly data still showed that more than seven in 100,000 children in that age group were admitted to hospitals — more than three times the rate of hospital admissions for children and teenagers ages 5 to 17.

Dr. Moira Szilagyi, the president of the American Academy of Pediatrics, said in a statement on Tuesday that she was encouraged that “we may be one step closer” to shots for the youngest children.

Last month, “we reported the highest number of Covid-19 cases among children since the pandemic’s onset. More than 3.5 million new cases in children were reported January 2022 alone,” she said. She urged “a transparent and data-driven process” in handling Pfizer’s request.

The C.D.C. released research in late December that showed very few reports of serious problems among children 5 to 11 who had received Pfizer-BioNTech shots.

But the pace of vaccination for America’s 28 million children in that age group has been even slower than public health experts had feared. Only about 30 percent of children in that age group have received at least one dose, according to C.D.C. data.

One study released by the C.D.C. of hundreds of pediatric hospitalizations in six cities last summer found that nearly all of the children who became seriously ill had not been fully vaccinated.

Apoorva Mandavilli contributed reporting. Kitty Bennett contributed research.